We will continue to focus on two experimental approaches that are proving useful in defining the origins of diversity and interrelationships that exist among the heterogeneous-mononuclear phagocytes. We will continue our characterization of bone marrow-derived macrophages (BMDMO) at various stages of growth in regard to ectoenzyme phenotypes, size distribution, certain cell-surface markers, and resistance to herpes simplex virus (HSV). The intrinsic interaction of HSV with BMDMO appears to be different from that with resident peritoneal MO (RES MO); this difference may be related to maturational differences between these two mononuclear phagocyte populations. We are developing methodology for molecular characterization of the HSV DNA species in various MO populations that are infected with HSV in order to determine whether the virus genome persists or whether abortive or defective virion production occurs. These studies will use new methodology of dot blot hybridization and Southern blot analysis with high specific activity HSV DNA probes. We will also be continuing to optimize our cell separation methodology using elutriation centrifugation, thus determining whether small size (e.g., immature) cells develop into larger (more mature) cells after various treatments. Our other experimental approach uses 89Sr to destroy bone marrow. We are defining the effects of this treatment on circulating, peritoneal, and splenic cell populations in regard to MO, natural killer and natural cytotoxic cells, and lymphocyte and polymorphonuclear leukocytes. Determination of ectoenzyme phenotypes of various MO using the two experimental approaches has led us to hypothesize that the RES MO may be a unique population. Research in this next year will prove the mechanisms involved in origin and maintenance of this population. (MB)